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头颈部侵袭性纤维瘤病1例

2019-08-21 李正强 刘曙光 口腔疾病防治

患者,男性,13岁,主诉因“右颈部无痛性肿物半年余”入院。入院查体:右侧颈上部皮肤稍隆起,皮温色泽正常,可触及一大小约3.5 cm×2.5 cm×3.0 cm肿物,前界位于胸锁乳突肌前缘前2.5 cm处,后界位于胸锁乳突肌前缘后1.0 cm处,上界达乳突,下界位于下颌下缘所在平面,表面光滑,活动度差,质硬,无触痛。入院前B超检查提示:右侧颈部皮下实质团块,待排良性间叶组织来源肿瘤。

侵袭性纤维瘤病(aggressive fibromatosis,AF),又称韧带样型纤维瘤病(desmoid-type fibromatosis)、韧带样瘤(desmoid tumor)、分化良好的非转移性纤维肉瘤(well-differentiated non metastasizing fibrosarcoma)、Ⅰ型纤维肉瘤(grade Ⅰ fibrosarcoma),是一种较为罕见的良性间质病变,起源于肌肉、筋膜、腱膜等结构,可表现为局部侵袭性生长,易局部复发,但无远处转移能力,其生物学行为和组织病理学表现介于良性纤维性病变和纤维肉瘤之间。任何年龄均可发病,青年高发,无性别差异。
 
根据发生部位,AF分为三型:腹外型、腹壁型和腹内型。腹外型发生在肩部、背部、四肢以及头颈部。头颈部青少年侵袭性纤维瘤病较为少见,国内报道较少,南方医科大学口腔医院于2017年8月收治1例发生于颈部的AF患者,现就该病例的特点进行报告并复习相关文献,对本病的病因、临床表现、病理学特点、治疗方法及预后进行探讨。
 
1.病例资料
 
患者,男性,13岁,主诉因“右颈部无痛性肿物半年余”入院。入院查体:右侧颈上部皮肤稍隆起,皮温色泽正常,可触及一大小约3.5 cm×2.5 cm×3.0 cm肿物,前界位于胸锁乳突肌前缘前2.5 cm处,后界位于胸锁乳突肌前缘后1.0 cm处,上界达乳突,下界位于下颌下缘所在平面,表面光滑,活动度差,质硬,无触痛。入院前B超检查提示:右侧颈部皮下实质团块,待排良性间叶组织来源肿瘤。
 
入院后核磁共振检查结果(图1)提示:右侧颈动脉鞘区后方、腮腺内侧、颈1~3椎体外侧可见一团状异常信号影,大小约2.9 cm×3.6 cm×5.0 cm,边缘光滑,其内多发点状低信号影,周围组织受推压改变。考虑神经纤维瘤?孤立性纤维瘤?入院初步诊断:右颈部肿物(性质待查)。



图1 核磁共振检查结果。肿物位于右侧颈动脉鞘区后方、腮腺内侧、颈1~3椎体外侧。a:横断面;b:冠状面。
 
入院完善术前常规检查,排除手术禁忌证后,于全麻下行“右颈部肿物探查术+术中冰冻病理检查”,术中见肿物位于颈鞘深面,可见Ⅱ区、Ⅲ区淋巴结肿大并呈串珠状,肿物与周围肌肉(肩胛提肌)黏连,切取部分肿物,可见肿物呈实性,剖面呈深灰色,未见明显液化,将切取的部分肿物与Ⅱ区、Ⅲ区肿大的淋巴结(图2a、图2b)送术中冰冻病理检查。术中病理结果示:右颈部梭形细胞肿瘤,瘤细胞未见明显异型性和坏死,考虑为良性病变,待免疫组化明确细胞分型,Ⅱ区、Ⅲ区淋巴结未见瘤细胞转移。继续分离肿物,可见其与第一颈椎横突相连,完整切除肿物(图2c、图2d),与之黏连的第一颈椎横突骨质未见吸收破坏,彻底止血后缝合伤口。



图2 术中图像。a:术中标记肿物大小及位置;b:术中可见肿物表面淋巴结肿大并呈串珠状;c:完整切除的肿物;d:术后创面。
 
术后病理结果如图3所示:送检组织呈结节样,无明显包膜,周边见少许脂肪细胞,灶性淋巴细胞浸润,梭形纤维细胞和纤维母细胞束状交错排列,部分透明样变,组织内见灶性萎缩的横纹肌,未见明显坏死;免疫组化瘤细胞HHF-35(+),Ki-67约3%(+),Vimentin(+),CD34(-),S-100(-),右颈部淋巴结未见瘤细胞转移,右颈部肿物符合侵袭性纤维瘤病,无明显周围肌肉组织浸润。根据术中术后病理结果以及肿瘤的临床表现,术后诊断为:右颈部侵袭性纤维瘤病。术后7d间断拆除伤口缝线。术后随访6个月未见复发。



图3 HE染色及免疫组织化学染色×200。a:HE染色可见肿瘤细胞呈长梭形排列成束状;b:HHF-35(+)免疫组化;c:Ki-67(+)免疫组化;d:Vimentin(+)免疫组化。
 
2.讨论
 
1832年MacFarlane首次报道了侵袭性纤维瘤病,2013年WHO将其归类为成纤维细胞/肌成纤维细胞性肿瘤中的具有局部侵袭性的中间性肿瘤。
 
2.1病因
 
AF的发病机制尚不明确,可能是一个多因素的致病过程,与创伤、内分泌、物理、遗传等因素有关。其细胞遗传学的改变包括trisomy-8、trisomy-20以及Y染色体的丢失。该病的发生可能和体细胞突变有关,突变主要发生在3P21上编码β-catenin基因(catenin beta 1,CTNNB1)的外显子3上的三个位点:T41A、S45F、aS45P。β-atenin主要调控细胞的粘附和基因转录,它在进入细胞核后和TBL1/TBLR1结合,从而促进Wnt/APC/β-atenin信号通路中相关目的基因的表达,如增殖因子S100A4或CTHRC1。突变影响了APC和β-catenin的相互作用位点,且导致β-atenin在细胞核内聚集发生异常,从而导致Wnt/APC/β-atenin通路信号转导发生障碍。该突变具有高度的特异性,未来可能用于辅助该病的诊断和预测复发率。
 
亦有最近的研究显示该病可能来源于间充质干细胞,β-atenin作用于间充质干细胞使其维持在一种低分化状态,从而促使该肿瘤的形成。本病例中患儿右侧颈部无创伤史,且无家族遗传史,发病原因可考虑为患儿青春期的内分泌变化等其他因素所致。
 
2.2临床表现
 
发生于头颈部软组织的AF约占全身AF的5%~9%。病变多见于儿童或年轻人,也可偶见于中年人。肿瘤可发生在头颈部任何部位,如下颌骨、上颌骨、舌、唇、颊、咽、颈部等。该病没有特异性的临床表现,通常表现为质硬、无痛性肿块(偶有疼痛),也可呈快速或隐蔽性生长,活动度差,多与周围的肌肉或骨骼有粘连。可导致明显的面部畸形,侵犯颅底或重要的神经血管、压迫呼吸道等严重的后果。术前辅助检查主要包括超声、CT、MRI等。MRI可作为术前判断病变大小和位置的首选方法,MRI多表现为等T1、稍长T2信号,病灶整体上信号均匀,瘤内见特征性的低T1及T2信号的胶原纤维成分对诊断具有一定提示作用,MRI增强扫描后多呈不均匀明显强化。
 
影像学引导下的细针吸取活检有助于术前确诊。本病例的临床表现符合典型的头颈部AF的临床表现,如“质硬、无痛、快速隐蔽性生长、活动度差”等,但AF的这些临床表现和其他肿瘤相比并无特异性,因此入院初步诊断并不能确诊为AF。AF是一种临界瘤,具有局部侵袭性,但本病例中MRI结果显示肿瘤边缘光滑、呈膨胀性生长压迫周围组织、周围软组织未见侵袭且邻近颈椎骨质未见吸收破坏,这可能和肿瘤的早期发现有关。AF通常起源于纤维结缔组织,本病例中可见肿瘤与周围的肩胛提肌及第一颈椎横突的骨膜相黏连,故推测本病例中肿瘤可能起源于周围的肩胛提肌或第一颈椎横突的骨膜。
 
2.3病理诊断
 
AF通常没有包膜(偶可见包膜),光镜下可见病变由等间距平行排列的成纤维细胞和肌纤维母细胞组成,这些细胞呈长梭形,并排列成流线型束状,伴有不同程度的胶原化。病变通常界限不清,细胞呈浸润性生长,常浸润至周围邻近正常组织。细胞膜界限不清,细胞质数量不等,可见正常的有丝分裂,瘤细胞未见明显异型性和坏死,染色浅,具有一个或两个小的泡状核,染色质浓聚不明显,细胞核淡染,细胞质稍嗜酸性。病变中的血管呈狭缝状或表现为较小的血管口径,周围包绕以较厚的纤维组织壁,也可见血管扩张。间质中可见肥大细胞,位于血管周围间隙,外周淋巴细胞聚集。
 
电子显微镜显示成纤维细胞和肌纤维母细胞内具有大量肿大的粗面内质网。同时也可以发生化生性骨化。纤维瘤病浸润骨骼肌时可以表现为损伤和再生的肌纤维具有多核深染,肌间线蛋白阳性,可被误诊为横纹肌溶解。病变细胞表达波形蛋白(Vimentin)、平滑肌肌动蛋白(SMA)、β-atenin,偶尔表达肌间线蛋白(desmin),但是缺乏h-钙结合蛋白、CD34、s100蛋白。CD117和血小板来源的生长因子α很少表达,P16通常呈阳性。可表达基质金属蛋白酶尤其是MMP-7,MMP-7的过表达和广泛的细胞核β广泛的细胞核表达阳性相关。Ki-67的表达与该肿瘤的复发呈正相关,其检测可作为监测肿瘤复发与否的良好指标。许多病例表现为雌二醇受体阳性,因此临床上抗雌二醇治疗是一种可考虑的治疗方法。
 
侵袭性纤维瘤病的病变细胞的细胞核β-atenin免疫组化阳性时,染色中可呈现为颗粒状物体,该颗粒的出现为诊断提供了极大的帮助,因为其他的显微镜下类似的肌纤维母细胞病变缺乏细胞核β粒状物体。然而在有一些肌纤维母细胞病变中,核旁的细胞质可染色可被误认为细胞核染色,这将导致该病的误诊。AF的确诊依赖于组织病理学,本病例的组织病理学特征与之相符,如:无包膜、排列成束状的长梭形细胞以及免疫组织化学染色结果等。
 
2.4治疗方法及预后
 
临床上侵袭性纤维瘤病的治疗目前其主要治疗方法仍是手术切除。其他的治疗方法包括局部放射治疗、化学治疗、激素治疗、生物治疗等,这些治疗措施在控制肿瘤生长或缩小肿瘤方面有一定的作用,但没有哪一种治疗方法在所有的病例中都有效果。有一些研究者认为:为了获得阴性切缘可能导致不必要的创伤及功能丧失,而且并不会阻止局部的复发,因此手术过程中应注重保存患者正常的组织结构和功能,且现有的证据并不能确切的证明残留病灶的存在会对5年复发率或者总生存率有影响。
 
然而,Fasching等观察到手术切除时的阳性边缘和局部复发率之间有着密切的联系,他们报道了48例头颈部侵袭性纤维瘤病的的回顾性研究,对于完整切除后的病例局部复发率为25%,而手术过程中没有完整切除的病例局部复发率高达80%。由于该病局部呈侵袭性生长,目前对于软组织纤维瘤病手术切除时是扩大切除,并且要保证有阴性的手术切缘,然而当肿瘤侵犯颈内动脉、颅底、臂丛神经等重要结构时,实行功能性切除对外科医生来说是一项挑战,此时肿瘤通常不能被完全切除。对于未完整切除、无法完整切除或复发的病例,有时可采用术后辅助放疗,否则肿瘤很容易复发。术后28d内总放疗剂量为56Gy时,局部控制率可达77%。
 
Sun等报导的1例病例中肿瘤侵犯了邻近的颈内静脉和颈外动脉,且即使切除了这些重要的解剖结构后也无法获得阴性边缘,所以患者术后随即接受了总剂量为50Gy的放疗,经过7个月的随访,没有发现复发。但因为放射线潜在的损害,因此对于儿童患者很少使用放射治疗。
 
本病例考虑到患者为青少年,且病变局限,可予以手术完整切除,故本病例中选择手术切除的方法来治疗。术中冰冻虽然提示为良性的梭形细胞肿瘤,但手术时仍然切除了与肿瘤黏连的部分肌肉以及第一颈椎横突的骨膜,因椎骨骨质表面光滑未见吸收破坏,故未行椎骨部分切除术。术后病理结果确诊为“侵袭性纤维瘤病”,但术中肿物切除彻底,故术后未予以辅助放疗等其他治疗。常用的激素治疗药物主要为三苯氧胺、促性腺激素释放激素激动剂、孕激素、芳香化酶抑制剂等。
 
一项134例的大样本回顾性研究显示使用激素治疗时可控制局部病灶。有时亦可和非甾体类抗炎药联合使用。三苯氧胺是一种抗雌激素药物,当它和苏灵大(sulindac)或塞来昔布(celecox-ib)联合使用时有时疗效会更为显著。在一项早期的研究中,对7位患者采用非甾体类抗炎药并联合使用睾内酯或三苯氧胺治疗时,有5位患者的肿瘤大部分消退,1位患者部分消退但肿瘤中央出现广泛性的液化坏死。在随后的一项研究中,使用三苯氧胺和塞来昔布联合治疗时,约有一半的病例肿瘤大小保持稳定或者缩小。化学治疗多采用单种或多种药物联合治疗,其疗效也不尽相同。在体外培养的纤维瘤病组织中,异环磷酰胺对病变细胞具有较好的抑制作用。
 
临床已经使用的治疗药物主要有阿霉素、甲氨蝶呤和长春花碱、阿霉素和达卡巴嗪。脂质体阿霉素亦可用于治疗无法切除的侵袭性纤维瘤病中。生物治疗在部分病例中效果较好,临床上常用的生物制剂为酪氨酸激酶抑制剂,主要包括伊马替尼和索拉非尼。临床上还可见部分病例可自行停止生长并保持稳定甚至逐渐缩小,因此有人建议对于这类病例应该不予以治疗,采用保守观察。
 
侵袭性纤维瘤病的患者应该保持长期的术后随访,因为复发通常发生在术后的前几年,与AF术后复发相关的因素主要包括年龄、肿瘤位置、大小以及是否被完整切除等,在同时患有家族性腺瘤性息肉病或加德纳综合征的年轻患者其复发率明显增加。Hools等建议随访应该基于前3年内每3个月的临床检查,随后的两年内每6个月复查1次,以后每12个月复查1次。当临床检查怀疑有肿瘤时或者病变太深无法检查时可借助CT和MRI检查。本病例中患者术后伤口愈合良好,随访过程中未见复发征象,嘱患者定期复诊,若后期出现复发,则需根据具体情况再次手术治疗或放疗,必要时可辅以其它治疗方法如化学治疗、激素治疗、生物治疗等。
 
综上所述,头颈部侵袭性纤维瘤病多有重要解剖结构参与或接近、呈浸润性生长、局部易复发,且目前尚缺乏最佳治疗方案,因此该病的发病机制及治疗仍需进一步研究。
 
原始出处:

李正强,刘曙光.头颈部侵袭性纤维瘤病1例及文献复习[J].口腔疾病防治,2018(09):592-597.

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    2021-07-10 久久归医

    学习了

    0

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    2019-08-23 sunyl07
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    2019-08-23 wshxjq
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头颈部鳞癌研究进展

美国临床肿瘤学会(ASCO)年会在芝加哥盛大开幕。作为全世界规模最大、学术水平最高、最具权威的临床肿瘤学术会议,大量最新研究进展在会上公布。头颈部鳞癌的临床治疗现状如何?有哪些最新的研究进展?来自同济大学附属东方医院的郭晔教授为您带来详细解读。

西妥昔单抗联合化疗能使中国复发/转移性头颈部鳞癌患者获益

2018年欧洲肿瘤内科学会亚洲年会(ESMO ASIA 2018)于11月23-25日在新加坡举行。欧洲肿瘤内科学会(ESMO)成立于1975年,是欧洲领先的肿瘤内科学专业组织;2018 ESMO亚洲年会致力于使亚太地区肿瘤学专业人士与快速发展的肿瘤学科学与教育保持同步。在今年的ESMO亚洲年会上,来自上海同济大学附属东方医院的郭晔教授就复发/转移头颈鳞癌的III期CHANGE-2研究结果做了口头

RadioGraphics:头颈部肉芽肿性疾病

RadioGraphics:头颈部肉芽肿性疾病

JAHA:胸部、头颈部放射治疗后癌症患者他汀类药物使用与血管事件风险

由此可见,放射治疗后使用他汀类药物与卒中显著减少有关,并且趋向于显著减少心血管和脑血管事件。

Int Oral Max Surg: 上臂内侧游离皮瓣在口腔修复中的应用

之前已经有研究提出用上臂内侧作为潜在的游离皮瓣供体部位,但是这种皮瓣在头颈部修复中的临床应用尚未普及。

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